This laboratory is involved in studies into the biochemistry of radiation induced DNA damage and its repair in human cells and the relationship of DNA repair to certain human genetic disorders that display cellular hypersensitivity to UV and a predisposition to cancer. In order to obtain a more detailed understanding of the molecular mechanisms of DNA repair in complex biological systems such as human cells, experiments are also being conducted with the simple eukaryote Saccharomyces cerevisiae. Most studies in this area have focused on the role of pyrimidine dimers, the predominant UV-induced DNA photoproduct. We are particularly interested in the nature and biological significance of a bifilar DNA lesion that is induced by ultraviolet radiation. Sensitive, quantitative assays developed in this lab will be used to investigate the chemical nature, photochemistry and biological significance of this lesion. It is expected that the bifilar nature of this photoproduct will require different repair processes than unifilar lesions such as pyrimidine dimers. It is therefore of interest to determine if the bifilar lesions are related to a variety of biological endpoints including cell killing, mutagenesis, recombination and neoplastic transformation. Deficiencies in the repair of these bifilar lesions might also provide a molecular explanation for the cellular hypersensitivity associated with certain human genetic disorders. Throughout these studies the properties of the bifilar sites and the mechanisms by which they are repaired will be compared with those of pyrimidine dimers, which are currently thought to be the critical UV-induced lesion.